tbuckley/cabot-search huggingface dataset:
Abstract 15039: International Multicenter Registry Study of Patients With Variants in <i>ATP1A3</i> -Encoded Sodium-Potassium ATPase 3 Finds an Association With Short QT and Life-Threatening Ventricular Arrhythmias
Authors: Mary E Moya-Mendez, Minu-Tshyeto Bidzimou, Jordan E Ezekian, Robin M Perelli, Lauren Parker, Lyndsey Prange, Jeffrey J Kim, Taylor S Howard, Gabriel Reyes Valenzuela, Roberto Caraballo, Giacomo Garone, Federico Vigevano, Sarah Weckhuysen, Charissa Millevert, Monica Troncoso, Mario Matamala, Simona Balestrini, Sanjay Sisodiya, Josephine Poole, Claudio Zucca, Eleni Panagiotakaki, Sébile Tchaicha, Julie Sauquet, Marta Zawadzka, Maria Mazurkiewicz-Beldzinska, Carmen Fons, Jennifer Anticona, Elisa De Grandis, Sergiu Groppa, Sandra Paryjas, Andrey Megvinov, ROSARIA VAVASSORI, Andrew P Landstrom
Journal: Circulation (2022)

Introduction: Variants in the ATP1A3 -encoded sodium-potassium ATPase-3 can result in Alternating Hemiplegia of Childhood (AHC), which was previously believed to primarily be a neurologic disease. Patients with ATP1A3 variants can experience sudden unexplained death (SUD) which has been linked with cardiac arrhythmias. Given that pathogenic variants in ATP1A3 are rare, the goal was to conduct a multicenter study to determine the impact of ATP1A3 variants on cardiac repolarization and lethal arrhythmia predisposition. Methods: This study was conducted by members of the International AHC Research Consortium (IAHCRC) according to the collaboration rules defined in the IAHCRC Charter. We analyzed 12-lead electrocardiograms from 134 patients from 12 centers across 7 countries. Of these patients, 120 had variants in ATP1A3 . Patients were grouped as follows: ATP1A3 variant status (positive vs. negative) and variant frequency (D801N vs. E815K vs. G947R vs. other). Blinded, manual measurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. The Gollob criteria was used to establish an abnormally short QTc measurement of &lt;370 ms. Results: QTcs were significantly shorter when comparing ATP1A3 variant positive patients to negative ( P =0.004). Patients with the ATP1A3 -D801N variant had significantly shorter QTcs compared to E815K, G947R, and all other less common variants ( P =0.0105, P =0.0234, P =0.0076, respectively). ATP1A3 -D801N variant average QTc was 363.9 ms and remained &lt;380 ms throughout adulthood for 68% of this population. Of the 34 patients with the ATP1A3 -D801N variant, 23 had short QTcs and 3 of those patients had ventricular tachycardia/ventricular fibrillation arrest, cardiac death, or an ICD implanted for exercise-induced syncope. Conclusions: In the largest study to date of the impact of ATP1A3 variants on the heart, we find that patients with ATP1A3 -D801N variants have shorter QTcs and are more likely to experience arrhythmias, which can cause syncope and even sudden death. The shortened QTc, which is a predisposing factor for the generation of ventricular arrhythmias, may underlie the SUD etiology in patients with AHC. Patients with variants in ATP1A3 should receive regular cardiac evaluation.
Abstract 15038: Collateral Flow From the Right Coronary Artery Alone is Not Sufficient for Adult Alcapa: Clinical Case Report
Authors: Liu CongYong, kuan zeng, Taihui Yu, Lu Zhang, Jianfen Li, Huiqi Jiang, Minnan Gao, Jingwen Li, Jingfeng Wang, Yanqi Yang
Journal: Circulation (2022)

Introduction: Myocardial ischemia in adult ALCAPA (Anomalous left coronary artery from the pulmonary artery) may lead to sudden death as the first clinical presentation. Cardiac blood supply from the right coronary artery alone is not sufficient for an adult ALCAPA. The aim of the present study was to describe a clinical case of severe myocardial ischemia in an adult female with ALCAPA supplied by the right coronary artery alone. Patient and Clinical data: 45-year-old female patient admitted to our hospital due to recurrent palpitation with tachypnoea after physical exertion for 2 years. Resting ECG on admission with ST-T changes and frequent premature ventricular contractions (PVC) indicated significant myocardial ischemia. Transthoracic echocardiography (TTE) showed dilated left ventricle (LVDd 64mm) with regional systolic dysfunction anterolateral and posterolateral with EF of 44% and dilated right coronary artery. An ALCAPA was observed with dilated caliber of 9 mm at ostium (Panel A) which was confirmed by computed tomographic angiography of the coronary artery and coronary angiography. Well-developed collateral vessels between peripheral right posterior descending (RPD) and distal left anterior descending (LAD) were demonstrated (Panel F). No collateral vessel was found between bronchial artery and ALCAPA. The bronchial arteries were visualized in normal size. The left coronary ostium was not found in the aortic root at aortography. The patient underwent anatomical reconstruction of left main coronary artery by using autologous pulmonary flap and recovered well postoperatively. Results: Postoperative ECG showed that the preoperative ST-T changes and PVC disappeared completely. Cardiac magnetic resonance imaging and TTE one month and 6 months postoperatively demonstrated continuously improved LV systolic function and myocardial perfusion posterolaterally and anterolaterally. Conclusion: Collateral flow from the right coronary artery alone is not sufficient for adult ALCAPA and completely surgical correction is necessary.
Abstract 15201: Empagliflozin Improves Baroreflex Sensitivity and Heart Function in Infarcted Rats
Authors: Bruno Durante da Silva, Leandro E de Souza, Maikon B da Silva, Bruno do Nascimento-Carvalho, Juliana Romeu Marques, Paulo M Dourado, Fernanda Columbo, Maria C Irigoyen
Journal: Circulation (2022)

Introduction: Several experimental studies have shown improvement in cardiac function of infarcted animals (diabetic or not) when treated with empagliflozin. Likewise, several clinical studies have shown improved outcomes in patients with heart failure with reduced ejection fraction or preserved ejection fraction in patients using empagliflozin. Methods: Wistar rats were divided into 2 groups: AMI - acute myocardial infarction (n=8) and EMPA - acute myocardial infarction + Empagliflozin (n=9).The animals of both groups were anesthetized and submitted to thoracotomy and ligature of the left coronary artery. The animals in the EMPA group received 10 mg/kg of empagliflozin daily through oral gavage for 14 days. After this period, an echocardiographic examination was performed, followed by cannulation of the femoral vein and artery, to evaluate hemodynamic parameters and baroreflex activity. Data were compared using unpaired t test or Mann-Whitney test and considered significant when p&lt;0,05. Results: In the echocardiographic evaluation, an improvement in the systolic function indices was observed in the EMPA group in comparison to the AMI group: SF (27.42% ± 3.117 vs 19.17% ± 0.857), EF (50.69% ± 4.848 vs 37.95% ± 1.528), FAC (38.46% ± 2.382 vs 23.65 ± 1.415), as well as diastolic function indices: E'/A' ratio (1.571 ± 0.156 vs 0.574 ± 0.040) E/E' ratio: (16.24 ± 2.461 vs 28.27 ± 2.788).A reduction in mean arterial pressure was observed in the EMPA group (85.96 mmHg ± 1.437) in comparison to the AMI group (92.21 mmHg ± 2.345).In addition, there was an improvement in the baroreflex mediated tachy and bradycardic responses in the treated animals: tachycardic response (4.957 bpm/mmHg ± 0.125 vs 3.243 bpm/mmHg ± 0.157) and bradycardic response (1.532 bpm/mmHg ± 0.058 vs 0.710 bpm/ mmHg ± 0.017). Conclusions: Empagliflozin treatment in infarcted rats improved left ventricular systolic and diastolic function and improved baroreflex sensitivity.
Abstract 15026: The Use of Artificial Intelligence Guidance for Rheumatic Heart Disease Screening by Novices
Authors: Daniel Peck, Craig A Sable, Doreen Nakagaayi, Joselyn Rwebembera, Neema Minja, Jafesi Pulle, Jennifer Klein, David Adams, Randolph Martin, Kilian Koepsell, Andrea Z Beaton
Journal: Circulation (2022)

Introduction: A novel technology utilizing artificial intelligence (AI) to provide real-time image-acquisition guidance, enabling novices to obtain diagnostic echocardiographic (echo) images holds promise to expand the reach of echo screening for rheumatic heart disease (RHD). We evaluated the ability of non-experts to obtain diagnostic quality images in patients with RHD using AI guidance (Caption Health) with color Doppler. Methods: This study was performed in Kampala, Uganda at the Uganda Heart Institute. Nurses and nursing students with no prior echo experience underwent one-day training in the use of AI guidance, which included a 7-view screening protocol with 2D and color Doppler images. Following training, all participants scanned 8-10 patients using AI guidance, half RHD and half normal. The same patients were scanned by two expert sonographers without the use of AI guidance. Each echo was evaluated by a panel of 4 expert echocardiographers blinded to the identity of the scanner (novice/exert) and diagnosis of the patient to provide quality assessment including (1) diagnostic quality to determine presence/absence of RHD, (2) more detailed valvular assessment, and (3) ACEP score 1-5 for each view. Results: Thirty-six novice scanners scanned a total of 50 patients, 25 with RHD and 25 controls. A total of 462 echocardiogram studies were obtained, 351 obtained by non-experts using AI guidance and 111 obtained by expert sonographers without AI guidance. Preliminary analysis of 394 interpretations showed that 95% of non-expert studies were of diagnostic quality to assess for RHD and mitral valve disease (vs 100% by experts, p=0.03), but only 56% of non-expert studies were of diagnostic quality to assess aortic valve disease (vs 97% by experts, p&lt;0.0001). The ACEP scores of non-expert images were highest in the parasternal long axis images (mean 3.62, 84% ≥ 3) compared to lower scores for apical 4 (mean 3.28, 73% ≥3), and apical 5 images (mean 2.52, 46% ≥ 3). Conclusions: AI guidance with color Doppler is feasible to enable rheumatic heart disease screening by non-experts, performing significantly better for assessment of the mitral than aortic valve. Further refinement is needed to optimize acquisition of color Doppler apical views.
Abstract 15021: Kinetics and Prognosis Value of Rantes (ccl5) at the Acute Phase of Stemi
Authors: simon leboube, Camille Brun, Florentin Moulin, Ahmad Hayek, Iyad Abousaleh, Alexandre Paccalet, Gilles Rioufol, Cyril PRIEUR, Eric BONNEFOY-CUDRAZ, Nathan O Mewton, Gabriel Bidaux, Melanie Paillard, Claire Crola Da Silva, Sylvie Ducreux, Thomas Bochaton
Journal: Circulation (2022)

Introduction: CCL5 or RANTES is a chemokine that mediates chemotaxis and activation of T cells, monocytes, granulocytes, mast cells and dendritic cells. It is involved in the pathogenesis of several diseases including atherosclerosis but little is known about its role at the acute phase of myocardial infarction (MI). Hypothesis: We questioned whether the serum level of RANTES might be a marker of the severity of acute MI. Methods: We prospectively enrolled 251 consecutive STEMI patients who underwent PCI into a prospective cohort. Blood samples were collected at 5 time points: admission, 4, 24, 48 hours and 1 month after admission (H4, H24, H48, M1). RANTES serum levels were assessed using an ELISA assay. Patients underwent cardiac magnetic resonance imaging at one month. Clinical outcomes were prospectively recorded over 12 months. Results: Mean age of the study population was 59±12 years and 54.6% patients exhibited anterior MI. Serum RANTES level raised from 12.6 [7.6-20.8] ng/mL at H0 to 13.9 [7.6-20.8] ng/mL at H4 and decreased gradually until 1 month at 9.3 [4.9-13.6] ng/mL (Kruskal-Wallis test, p&lt;0.0001). RANTES area under curve (AUC) level was not correlated with IS (r =-0.03, p=0.70) or LVEF assessed by MRI (r=0.02, p=0.80). Patient with a RANTES AUC serum level below the first tertile value of the population (411.0 ng.h.mL -1 ) were more likely to have a MACE during the first 12 months after STEMI (hazard ratio at 2.9 (1.3-6.6), p=0.01). In a multivariable Cox regression analyses with a model including age, gender, troponin peak, and TIMI flow grade after PCI, RANTES AUC serum level below the first tertile remained associated with an increased risk of experiencing MACE during the 12 months of follow-up (adjusted HR = 2.6 (1.2-5.8), p=0.02) Conclusion: A low level of circulating RANTES at the acute phase of STEMI was independently associated with an increased risk of experiencing MACE in our population. Serum RANTES might be a valuable prognostic marker in STEMI patients.
Abstract 15032: Association of Race, Socioeconomic Status, and Incident Heart Failure: An Analysis of the National Health and Nutrition Examination Survey (nhanes)
Authors: Stanley Aladi, Quentin Youmans, Rebecca Harap, Tingqing Wu, Alana A Lewis, Logan Brown, Sabra Lewsy, Kamari Jackson, Jennifer Maning, Cheryl N Mensah, Oluseyi Ojeifo, Clyde W Yancy, Ike Okwuosa
Journal: Circulation (2022)

Background: Black Americans are disproportionately affected by heart failure (HF), including higher age adjusted mortality rates. Socioeconomic factors have been implicated as a driver of risk. This study seeks to further define the association of socioeconomic factors and risk of HF in a large heterogeneous cohort. Methods: This was an analysis of 58,555 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999-2020. Participants were categorized by race and socioeconomic factors including education level and income. Education level was subdivided into high school education or less, and some college and greater. Using the income to poverty ratio (I/P), we defined three tiers of household income. High tier (I/P &gt;2), Middle Tier (I/P 1.0-1.9), and low tier (I/P &lt;1). Outcome variables were defined based on both examination data and survey questionnaire responses. Logistic regression was performed to ascertain odds ratios (OR) with 95% confidence intervals (CI). Results: In multivariable analysis, factors such as age (OR 1.06, CI 1.06-1.07; p=&lt;.0001), and self-reported Black race (OR 1.2, CI 1.02-1.4; p=&lt;.0001), were associated with incident HF. Medium tier (OR 1.5, CI 1.35-1.87; p= &lt;.0001) and low tier household income (OR 1.7, CI 1.42-2.09; p= &lt;.0001) had a higher odds of HF compared to high tier household income. Intra-racial multivariable analysis showed that among Black participants, low tier household income (OR 1.8, CI 1.2-2.6; p=0.001) was associated with incident HF. No difference among gender or education attainment was observed. Interracial multivariable analysis based on household income showed that Black participants in the low tier of household income (OR 1.36, CI 1.01-1.85; p=0.04) had an increased odds of HF compared to Non-Black at similar household income. Black and Non-Black participants had similar odds of HF at medium and high tier household incomes. Conclusion: In this analysis, Black participants had higher odds of incident HF compared to other participants. Factoring in household income, Black participants in the lowest income tier were the most vulnerable. Targeting income inequality may help address racialized HF disparities.
Abstract 15083: Chronicity of Heart Failure, In-Hospital Clinical Trajectory, and Post-Discharge Outcomes Among Patients Hospitalized for Heart Failure
Authors: Jacob B Pierce, Muhammad H Maqsood, Mohammad S Khan, Abdul M Minhas, Michael Felker, Stephen J Greene
Journal: Circulation (2022)

Introduction: Among patients hospitalized for HF, patients hospitalized with worsening chronic heart failure (WCHF) are at increased risk for morbidity and mortality compared with those who are recently diagnosed with HF. Whether there are differences in clinical course during hospitalization for HF is unclear. Methods: We pooled 735 participants hospitalized for HF in the DOSE, CARRESS, and ROSE trials. We grouped participants by whether HF was recently diagnosed (≤12 months) or WHCF (&gt;12 months). We compared changes in congestion, kidney function, and symptoms during hospitalization, as well as early post-discharge kidney and mortality outcomes. Results: Overall, 132 (18%) had recently diagnosed HF and 603 (82%) had WCHF. Compared with WCHF, patients with recently diagnosed HF tended to have lower serum creatinine and higher systolic blood pressure, ejection fraction, and serum NT-proBNP (all p&lt;0.05). In the first 72 hours, changes in body weight, global well-being visual analog scale, serum creatinine, and serum NT-proBNP, as well as net fluid loss were similar between patients with recently diagnosed versus WCHF (all p&gt;0.15) ( Figure ). Recently diagnosed HF showed improved dyspnea at 72 hours (p=0.03). There was no difference in change in serum creatinine from baseline to 60 days (p=0.75). There was a trend toward significantly increased odds of mortality during study follow-up (adjusted odds ratio 1.96 [95% confidence interval 0.97-3.94], p=0.06). Conclusion: Patients hospitalized for recently diagnosed and WCHF have generally similar in-hospital clinical trajectories, and similar changes in kidney function early post-discharge. Despite these similarities and adjustment for other clinical factors, patients with WCHF remain at increased risk for post-discharge mortality as compared with patients who are more recently diagnosed.
Watching the clock in glioblastoma
Authors: Priscilla Chan, Jeremy N Rich, Steve A Kay
Journal: Neuro-Oncology (2023)

Abstract Glioblastoma (GBM) is the most prevalent malignant primary brain tumor, accounting for 14.2% of all diagnosed tumors and 50.1% of all malignant tumors, and the median survival time is approximately 8 months irrespective of whether a patient receives treatment without significant improvement despite expansive research (Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015–2019. Neurooncology. 2022; 24(suppl 5):v1–v95.). Recently, important roles for the circadian clock in GBM tumorigenesis have been reported. Positive regulators of circadian-controlled transcription, brain and muscle ARNT-like 1 (BMAL1), and circadian locomotor output cycles kaput (CLOCK), are highly expressed also in GBM and correlated with poor patient prognosis. BMAL1 and CLOCK promote the maintenance of GBM stem cells (GSCs) and the establishment of a pro-tumorigenic tumor microenvironment (TME), suggesting that targeting the core clock proteins may augment GBM treatment. Here, we review findings that highlight the critical role the circadian clock plays in GBM biology and the strategies by which the circadian clock can be leveraged for GBM treatment in the clinic moving forward.
Effect of Dexmedetomidine on Posttraumatic Stress Disorder in Patients Undergoing Emergency Trauma Surgery
Authors: Youjia Yu, Yan Li, Dan Han, Chuhao Gong, Liwei Wang, Beiping Li, Rui Yao, Yangzi Zhu
Journal: JAMA Network Open (2023)

Posttraumatic stress disorder (PTSD) is common in people who have experienced trauma, especially those hospitalized for surgery. Dexmedetomidine may reduce or reverse the early consolidation and formation of conditioned fear memory and prevent the occurrence of postoperative PTSD. To evaluate the effects of intraoperative and postoperative low-dose intravenous pumping dexmedetomidine on PTSD among patients with trauma undergoing emergency surgery. This double-blind, randomized clinical trial was conducted from January 22 to October 20, 2022, with follow-up 1 month postoperatively, in patients with trauma undergoing emergency surgery at 4 hospital centers in Jiangsu Province, China. A total of 477 participants were screened. The observers were blinded to patient groupings, particularly for subjective measurements. Dexmedetomidine or placebo (normal saline) was administered at a maintenance dose of 0.1 μg/kg hourly from the start of anesthesia until the end of surgery and at the same rate after surgery from 9 pm to 7 am on days 1 to 3. The primary outcome was the difference in the incidence of PTSD 1 month after surgery in the 2 groups. This outcome was assessed with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (CAPS-5). The secondary outcomes were the pain score within 48 hours and 1 month postoperatively; incidence of postoperative delirium, nausea, and pruritus; subjective sleep quality; anxiety; and occurrence of adverse events. A total of 310 patients (154 in the normal saline group and 156 in the dexmedetomidine group) were included in the modified intention-to-treat analysis (mean [SD] age, 40.2 [10.3] years; 179 men [57.7%]). The incidence of PTSD was significantly lower in the dexmedetomidine group than in the control group 1 month postoperatively (14.1% vs 24.0%; P = .03). The participants in the dexmedetomidine group had a significantly lower CAPS-5 score than those in the control group (17.3 [5.3] vs 18.9 [6.6]; mean difference, 1.65; 95% CI, 0.31-2.99; P = .02). After adjusting for potential confounders, the patients in the dexmedetomidine group were less likely to develop PTSD than those in the control group 1 month postoperatively (adjusted odds ratio, 0.51; 95% CI, 0.27-0.94; P = .03). In this randomized clinical trial, the administration of intraoperative and postoperative dexmedetomidine reduced the incidence of PTSD among patients with trauma. The findings of this trial support the use of dexmedetomidine in emergency trauma surgery. Chinese Clinical Trial Register Identifier: ChiCTR2200056162.